RESUMEN
OBJECTIVE: To identify a possible functional imaging biomarker sensitive to the earliest neural changes in premanifest Huntington disease (preHD), allowing early therapeutic approaches aimed at preventing or delaying clinical onset. METHODS: Sixteen preHD and 18 healthy participants were submitted to anatomical acquisitions and functional MRI (fMRI) acquisitions during the execution of the exogenous covert orienting of attention task. Due to strong a priori hypothesis, all fMRI correlation analyses were restricted to the following: (1) the frontal oculomotor cortex identified by the means of a prosaccadic task, comprising frontal eye fields and supplementary frontal eye fields; and (2) the data collected during inhibition of return, a phenomenon occurring during the executed task. In preHD, multiple regression analysis was performed between fMRI data and the probability to develop the disease in the next 5 years (p5HD). Moreover, mean blood oxygen level-dependent (BOLD) signal changes in the frontal oculomotor cortex and striatal volumes were linearly correlated with p5HD. RESULTS: In preHD, multiple regression analysis showed that clusters of activity strongly correlated with p5HD in the right frontal oculomotor cortex. Importantly, mean BOLD signal changes of this region correlated with p5HD (r(2) = 0.52). Among the considered striatal volumes, a modest correlation (r(2) = 0.29) was observed in the right putamen and p5HD. CONCLUSION: fMRI activations in the right-frontal oculomotor cortex during inhibition of return can be considered a possible functional imaging biomarker in preHD.